Both NK cell-intrinsic and -extrinsic STAT1 signaling are required for NK cell response against vaccinia virus.
Both NK cell-intrinsic and -extrinsic STAT1 signaling are required for NK cell response against vaccinia virus.
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DOI：
10.4049/jimmunol.1202714
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发表时间：
2013-07-01
期刊：
影响因子：
--
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Fortin C;Huang X;Yang Y
NK细胞在痘苗病毒（VV）感染的天然免疫控制中起重要作用。然而，它仍然是不完全确定的NK细胞的激活响应VV是如何调节的。在这项研究中，我们发现STAT1是VV感染后NK细胞活化和随后清除体内VV感染的关键。我们进一步证明，在VV感染后，NK细胞和辅助细胞如DC中的STAT1信号传导是有效激活NK细胞所必需的。从机制上讲，DC中的STAT1信号传导促进了NKG2D配体的表达，这是通过NKG2D途径激活NK细胞所必需的。综上所述，我们的数据表明，STAT1介导的抗VV效应，通过促进NK细胞激活通过NK细胞的内在和外在机制，并可能提供见解设计有效的NK细胞为基础的治疗病毒感染。
NK cells play an important role in innate immune control of the infection with vaccinia virus (VV). However, it remains incompletely defined how the activation of NK cells in response to VV is regulated. In this study, we showed that STAT1 was critical for NK cell activation upon VV infection and the subsequent clearance of VV infection in vivo. We further demonstrated that STAT1 signaling in both NK and accessory cells such as DCs was required for efficient NK cell activation upon VV infection. Mechanistically, STAT1 signaling in DCs promoted the expression of NKG2D ligands, which is required for NK cell activation via the NKG2D pathway. Taken together, our data suggest that STAT1 mediates anti-VV effect by promoting NK cell activation through both NK-intrinsic and extrinsic mechanisms and may provide insights into the design of effective NK cell-based therapies for viral infections.
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